TY - JOUR
T1 - Effect of serotonin transporter genotype on carbon dioxide-induced fear-related behavior in mice
AU - Leibold, Nicole K.
AU - van den Hove, Daniel L. A.
AU - Weidner, Magdalena T.
AU - Buchanan, Gordon F.
AU - Steinbusch, Harry W. M.
AU - Lesch, Klaus-Peter
AU - Schruers, Koen R. J.
N1 - Funding Information:
The authors thank Denise Hermes, Barbie Machiels, Marjan Philippens, and Hellen Steinbusch for their technical assistance. They also thank the Boehringer Ingelheim Fonds, Deutsche Forschungsgemeinschaft (DFG: CRC TRR 58 A5, CRU 125, CRC TRR 58 A1/A5, No. 44541416), the European Union?s Horizon 2020 Research and Innovation Programme (Grant No. 728018, Eat2beNICE), ERA-Net NEURON/RESPOND (No. 01EW1602B), ERA-Net NEURON/DECODE (No. 01EW1902), 5-100 Russian Academic Excellence Project, NIH/NINDS (K08 NS069667) and the Beth and Nate Tross Epilepsy Research Fund for their financial support. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: NL was financially supported by the Boehringer Ingelheim Fonds, Germany, Daniel van den Hove (DvdH) by the Deutsche Forschungsgemeinschaft (DFG: CRC TRR 58 A5). GB was supported by NIH/NINDS K08 NS069667 and the Beth and Nate Tross Epilepsy Research Fund. KPL was supported by the Deutsche Forschungsgemeinschaft (DFG: CRU 125, CRC TRR 58 A1/A5, No. 44541416), the European Union?s Horizon 2020 Research and Innovation Programme under Grant No. 728018 (Eat2beNICE), ERA-Net NEURON/RESPOND, No. 01EW1602B, ERA-Net NEURON/DECODE, No. 01EW1902 and 5-100 Russian Academic Excellence Project. The funders had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Funding Information:
The authors thank Denise Hermes, Barbie Machiels, Marjan Philippens, and Hellen Steinbusch for their technical assistance. They also thank the Boehringer Ingelheim Fonds, Deutsche Forschungsgemeinschaft (DFG: CRC TRR 58 A5, CRU 125, CRC TRR 58 A1/A5, No. 44541416), the European Union’s Horizon 2020 Research and Innovation Programme (Grant No. 728018, Eat2beNICE), ERA-Net NEURON/RESPOND (No. 01EW1602B), ERA-Net NEURON/DECODE (No. 01EW1902), 5-100 Russian Academic Excellence Project, NIH/NINDS (K08 NS069667) and the Beth and Nate Tross Epilepsy Research Fund for their financial support.
Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: NL was financially supported by the Boehringer Ingelheim Fonds, Germany, Daniel van den Hove (DvdH) by the Deutsche Forschungsgemeinschaft (DFG: CRC TRR 58 A5). GB was supported by NIH/NINDS K08 NS069667 and the Beth and Nate Tross Epilepsy Research Fund. KPL was supported by the Deutsche Forschungsgemeinschaft (DFG: CRU 125, CRC TRR 58 A1/A5, No. 44541416), the European Union’s Horizon 2020 Research and Innovation Programme under Grant No. 728018 (Eat2beNICE), ERA-Net NEURON/RESPOND, No. 01EW1602B, ERA-Net NEURON/DECODE, No. 01EW1902 and 5-100 Russian Academic Excellence Project. The funders had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Publisher Copyright:
© The Author(s) 2020.
PY - 2020/12
Y1 - 2020/12
N2 - Background:Inhaling 35% carbon dioxide induces an emotional and symptomatic state in humans closely resembling naturally occurring panic attacks, the core symptom of panic disorder. Previous research has suggested a role of the serotonin system in the individual sensitivity to carbon dioxide. In line with this, we previously showed that a variant in the SLC6A4 gene, encoding the serotonin transporter, moderates the fear response to carbon dioxide in humans. To study the etiological basis of carbon dioxide-reactivity and panic attacks in more detail, we recently established a translational mouse model.Aim:The purpose of this study was to investigate whether decreased expression of the serotonin transporter affects the sensitivity to carbon dioxide.Methods:Based on our previous work, wildtype and serotonin transporter deficient (+/-, -/-) mice were monitored while being exposed to carbon dioxide-enriched air. In wildtype and serotonin transporter +/- mice, also cardio-respiration was assessed.Results:For most behavioral measures under air exposure, wildtype and serotonin transporter +/- mice did not differ, while serotonin transporter -/- mice showed more fear-related behavior. Carbon dioxide exposure evoked a marked increase in fear-related behaviors, independent of genotype, with the exception of time serotonin transporter -/- mice spent in the center zone of the modified open field test and freezing in the two-chamber test. On the physiological level, when inhaling carbon dioxide, the respiratory system was strongly activated and heart rate decreased independent of genotype.Conclusion:Carbon dioxide is a robust fear-inducing stimulus. It evokes inhibitory behavioral responses such as decreased exploration and is associated with a clear respiratory profile independent of serotonin transporter genotype.
AB - Background:Inhaling 35% carbon dioxide induces an emotional and symptomatic state in humans closely resembling naturally occurring panic attacks, the core symptom of panic disorder. Previous research has suggested a role of the serotonin system in the individual sensitivity to carbon dioxide. In line with this, we previously showed that a variant in the SLC6A4 gene, encoding the serotonin transporter, moderates the fear response to carbon dioxide in humans. To study the etiological basis of carbon dioxide-reactivity and panic attacks in more detail, we recently established a translational mouse model.Aim:The purpose of this study was to investigate whether decreased expression of the serotonin transporter affects the sensitivity to carbon dioxide.Methods:Based on our previous work, wildtype and serotonin transporter deficient (+/-, -/-) mice were monitored while being exposed to carbon dioxide-enriched air. In wildtype and serotonin transporter +/- mice, also cardio-respiration was assessed.Results:For most behavioral measures under air exposure, wildtype and serotonin transporter +/- mice did not differ, while serotonin transporter -/- mice showed more fear-related behavior. Carbon dioxide exposure evoked a marked increase in fear-related behaviors, independent of genotype, with the exception of time serotonin transporter -/- mice spent in the center zone of the modified open field test and freezing in the two-chamber test. On the physiological level, when inhaling carbon dioxide, the respiratory system was strongly activated and heart rate decreased independent of genotype.Conclusion:Carbon dioxide is a robust fear-inducing stimulus. It evokes inhibitory behavioral responses such as decreased exploration and is associated with a clear respiratory profile independent of serotonin transporter genotype.
KW - Panic attacks
KW - panic disorder
KW - serotonin transporter
KW - carbon dioxide
U2 - 10.1177/0269881120959611
DO - 10.1177/0269881120959611
M3 - Article
C2 - 33103571
SN - 0269-8811
VL - 34
SP - 1408
EP - 1417
JO - Journal of Psychopharmacology
JF - Journal of Psychopharmacology
IS - 12
ER -